{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T11:03:24Z","timestamp":1784372604898,"version":"3.55.0"},"reference-count":24,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T00:00:00Z","timestamp":1784332800000},"content-version":"vor","delay-in-days":198,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Tropical Medicine"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:p>\n                    Infantile tremor syndrome (ITS), a self\u2010limiting disorder prevalent in the Indian subcontinent, is characterized by tremors, anemia, pigmentary skin changes, developmental delay or regression, and hypotonia. Although a nutritional etiology is suspected, particularly vitamin B12 deficiency, the roles of the bioactive marker holo\u2010transcobalamin (holo\u2010TC) and essential fatty acids (EFAs) remain unexplored. This comparative pilot study was conducted from December 1, 2023, to April 30, 2024, at Government Medical College, Datia, India. The study included 14 infants who were assigned to two groups. Group 1 (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20097) comprised infants with ITS and tremors, and Group 2 (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20097) included those with ITS without tremors to assess threshold\u2010dependent biochemical markers across this clinical spectrum. Laboratory investigations included complete hemogram, serum vitamin B12, holo\u2010TC, and EFA profiles. Data were summarized using medians and interquartile ranges. Between\u2010group differences were expressed as effect sizes (median differences) with 95% confidence intervals. Severe developmental delays were more frequent in Group 1 (5\/7) than in Group 2 (mild to moderate in 4\/7). Both groups were anemic and had low serum vitamin B12 levels (median: 188\u2009pg\/mL in Group 1 vs. 198\u2009pg\/mL in Group 2). Holo\u2010TC was undetectable (&lt;\u20095\u2009pmol\/L) in Group 1 and in only one patient from Group 2 (median: 10.12\u2009pmol\/L in the remaining Group 2 patients). Macrocytosis was higher in Group 1 (median MCV: 98\u2009fL vs. 75.5\u2009fL), with a median difference of 22.5\u2009fL (95% CI: 6.8 to 38.2). Clinical examination also revealed characteristic hair hypochromotrichia and progressive regression in both phenotypes. Both groups exhibited low omega (\n                    <jats:italic>\u03c9<\/jats:italic>\n                    )\u20103 fatty acid levels, elevated saturated fatty acid levels, and high\n                    <jats:italic>\u03c9<\/jats:italic>\n                    \u20106:\u03c9\u20103 ratios (median: approximately 10:1), with small and imprecise between\u2010group differences (confidence intervals crossing zero). Extremely low holo\u2010TC levels were strongly associated with tremors in ITS, suggesting that holo\u2010TC is a superior marker of bioactive vitamin B12 deficiency and a critical metabolic threshold for tremor manifestation. EFA imbalances were prevalent in both groups but not specific to tremor incidence, highlighting the need for larger studies. The overall pathophysiology points toward significant maternal nutritional depletion during pregnancy and lactation as the relevant origin of the syndrome.\n                  <\/jats:p>","DOI":"10.1155\/jotm\/3144439","type":"journal-article","created":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T10:12:49Z","timestamp":1784369569000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Unveiling Nutritional Disparities in Infantile Tremor Syndrome: A Focus on Holo\u2010Transcobalamin and Essential Fatty Acids"],"prefix":"10.1155","volume":"2026","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0755-7704","authenticated-orcid":false,"given":"Rajesh","family":"Gupta","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6529-3850","authenticated-orcid":false,"given":"Puneet","family":"Agrawal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-1200-8104","authenticated-orcid":false,"given":"Jyoti","family":"Gupta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3002-5746","authenticated-orcid":false,"given":"Jyoti","family":"Singh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7576-895X","authenticated-orcid":false,"given":"Ashish","family":"Pathak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,18]]},"reference":[{"key":"e_1_2_12_1_2","doi-asserted-by":"publisher","DOI":"10.2147\/rrtm.s180604"},{"key":"e_1_2_12_2_2","first-page":"249","article-title":"Infantile Tremor Syndrome\u2013down but Not Out","volume":"52","author":"Goraya J. S.","year":"2015","journal-title":"Indian Pediatrics"},{"key":"e_1_2_12_3_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmolb.2016.00027"},{"key":"e_1_2_12_4_2","doi-asserted-by":"publisher","DOI":"10.1136\/adc.77.2.137"},{"key":"e_1_2_12_5_2","doi-asserted-by":"publisher","DOI":"10.1017\/S0007114518000090"},{"key":"e_1_2_12_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/85.4.1057"},{"key":"e_1_2_12_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2018.04.049"},{"key":"e_1_2_12_8_2","doi-asserted-by":"publisher","DOI":"10.18203\/2394-6040.ijcmph20233487"},{"key":"e_1_2_12_9_2","article-title":"WHO Child Growth Standards: Length\/Height-for-Age, Weight-for-Age, Weight-for-Length, Weight-for-Height and Body Mass Index-for-Age","author":"World Health Organization","year":"2006","journal-title":"Methods and Development"},{"key":"e_1_2_12_10_2","first-page":"297","article-title":"Further Observations on Infantile Tremor Syndrome","volume":"5","author":"Bajpai P. C.","year":"1968","journal-title":"Indian Pediatrics"},{"key":"e_1_2_12_11_2","doi-asserted-by":"publisher","DOI":"10.7860\/JCDR\/2018\/29522.11240"},{"key":"e_1_2_12_12_2","doi-asserted-by":"publisher","DOI":"10.1515\/cclm-2024-0692"},{"key":"e_1_2_12_13_2","first-page":"239","article-title":"The Syndrome of Tremors, Mental Regression and Anaemia in Infants and Young Children: A Study of 102 Cases","volume":"2","author":"Sachdev K. K.","year":"1965","journal-title":"Indian Pediatrics"},{"key":"e_1_2_12_14_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF02343237"},{"key":"e_1_2_12_15_2","doi-asserted-by":"publisher","DOI":"10.1007\/s13312-016-0918-9"},{"key":"e_1_2_12_16_2","doi-asserted-by":"publisher","DOI":"10.1136\/adc.67.8.1030"},{"key":"e_1_2_12_17_2","doi-asserted-by":"publisher","DOI":"10.1186\/s41936-020-00148-0"},{"key":"e_1_2_12_18_2","doi-asserted-by":"publisher","DOI":"10.1145\/245108.245124"},{"key":"e_1_2_12_19_2","doi-asserted-by":"publisher","DOI":"10.1177\/0883073814550828"},{"key":"e_1_2_12_20_2","doi-asserted-by":"publisher","DOI":"10.4103\/mjdrdypu.mjdrdypu_1247_24"},{"key":"e_1_2_12_21_2","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/54.3.438"},{"key":"e_1_2_12_22_2","doi-asserted-by":"publisher","DOI":"10.5223\/pghn.2019.22.2.171"},{"key":"e_1_2_12_23_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10803-021-05335-8"},{"key":"e_1_2_12_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.clnesp.2024.05.011"}],"container-title":["Journal of Tropical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1155\/jotm\/3144439","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1155\/jotm\/3144439","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1155\/jotm\/3144439","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T10:12:52Z","timestamp":1784369572000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1155\/jotm\/3144439"}},"subtitle":[],"editor":[{"given":"Priya","family":"Gusain","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,1]]},"references-count":24,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["10.1155\/jotm\/3144439"],"URL":"https:\/\/doi.org\/10.1155\/jotm\/3144439","archive":["Portico"],"relation":{},"ISSN":["1687-9686","1687-9694"],"issn-type":[{"value":"1687-9686","type":"print"},{"value":"1687-9694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1]]},"assertion":[{"value":"2026-03-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-01","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-18","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"3144439"}}